Methods and compounds for treating brain amyloidosis

Abstract

The present invention discloses the use of (i) a fragment of the amyloid precursor protein (APP); or, (ii) a derivative of (i); or, (iii) a functional mimetic of (i) or (ii), in the preparation of a medicament for modulating CNS levels and/or activity of a member of the neprilysin family.

1 - 38 . (canceled)  
     
     
         39 . A method of treating a neurodegenerative disorder, wherein the neurodegenerative disorder is brain amyloidosis or Alzheimer's disease, comprising increasing neutral endopeptidase-24.11 activity in a patient by administering to the patient a medicament containing 
 i) a fragment of the amyloid precursor protein,    ii) a derivative of the amyloid precursor protein obtained by varying the amino acid sequence of the fragment, or    iii) a functional mimetic of the fragment or the derivative.    
     
     
         40 . The method of  claim 39  wherein the neurodegenerative disorder is brain amyloidosis.  
     
     
         41 . The method of  claim 39  wherein the neurodegenerative disorder is Alzheimer's disease.  
     
     
         42 . The method of  claim 39  wherein CNS levels of neutral endopeptidase-24.11 are increased.  
     
     
         43 . The method of  claim 39  wherein neuronal or glial levels of neutral endopeptidase-24.11 are increased.  
     
     
         44 . The method of  claim 39  wherein the fragment comprises an amino acid sequence of an extracellular and a membrane-spanning region of the amyloid precursor protein.  
     
     
         45 . The method of  claim 39  wherein the fragment comprises a peptide of 38 to 43 amino acid length obtainable by proteolytic cleavage of the amyloid precursor protein using β- and/or γ-secretase.  
     
     
         46 . The method of  claim 39  wherein the fragment comprises the Aβ 1-42  peptide.  
     
     
         47 . The method of  claim 39  wherein the fragment comprises the Aβ 1-40  peptide.  
     
     
         48 . The method of  claim 39  wherein the medicament contains the fragment, derivative, or functional mimetic in the form of a monomer or multimer.  
     
     
         49 . The method of  claim 39  wherein the medicament contains the fragment, derivative, or functional mimetic in aggregated form.  
     
     
         50 . The method of  claim 39  wherein the medicament contains the fragment, derivative, or functional mimetic in aggregated form as fibrils.  
     
     
         51 . The method of  claim 39  wherein the fragment, derivative, or functional mimetic is synthetic.